New Protocol Managed to Create Kidney Cells in The Laboratory

A mature podocyte, colored purple, grows long extensions of its cell body known as “feet” that wrap around the kidney’s blood vessels and help filter impurities from the blood. Credit: Wyss Institute at Harvard University

Podocytes are the cells of the kidney which are highly specialized terminally differentiated and are present in the Bowman’s capsule of the kidney.

A new study led by the team of researchers from Wyss Harward university led to new protocol with the help of which a large number of mature human podocytes can be produced which in turn can lead to kidney disease modeling, drug discovery, and potential cell therapies

Human stem cells which occur naturally can reproduce and differentiate into any type of cell which makes it great interest in the fields of regenerative medicine and medical research. While the other cell called induced pluripotent stem cells (iPS cells) can be produced directly from adult cells these iPS cells offer the potential for a patient to one day have a limitless source of personalized cells to replace those lost to damage or disease.

Samira Musah, Ph.D., first author of the study, holds a Kidney Chip seeded with endothelial and glomerular cells. Credit: Wyss Institute at Harvard University

In their Previous studies, the researchers determined a protocol for generating human kidney podocytes (a type of cell that helps filter blood in the kidneys) from iPS cells with greater than 90% efficiency. Later on, they used those podocytes in a Glomerulus Chip for recreating specialized tissue structure and molecular filtration found in the glomerulus of the human kidney in the laboratory.

During their study using the same protocol, researchers demonstrated that the cells which were recreated after the differentiation of iPS cells have same transcriptomic and protein expression profiles compared to mature podocytes.

In the light of this study, kidney researchers across the scientific community can receive a tool which can help them to examine the function of the human kidney and its development. Additionally, Kidney diseases can also be investigated. These cells also could potentially be delivered as a cell therapy for kidney diseases in the future. The research is reported in Nature Protocols.

The induced progenitor cells first differentiate into progenitor cells which have the ability to divide into multiple types of cells. After that, the cells whose destiny is to become podocyte differentiate into nephron progenitor-like cells.

In the laboratory, These nephron progenitor cells can be used to mimic human cells but Before settling on their final cell type, iPS cells differentiate into “progenitor” cells, which can themselves become multiple cell types. Those that are destined to become podocytes first differentiate into nephron progenitor-like cells but mature cells are of much greater use to researchers and clinicians, as they more closely mimic the cells found in adult organs. Hence Researchers produced nephron progenitor-like cells from iPS cells followed by growing them in new cell culture medium which contains a cocktail of five molecules that had been previously shown to play key roles in kidney development and function in vivo.

This protocol of creating podocyte can help to investigate many kidney diseases like to find their source and all the steps involved in the differentiation of podocytes from their progenitor cells (a process which remains largely unknown). It also shows potential for establishing in vitro systems for kidney drug testing and discovery, such as the Glomerulus Chip. The researchers also assume that mature human iPS cell-derived podocytes could one day be used as an injectable form of cell therapy for diseases that are characterized by podocyte loss or dysfunction.

“This method for generating mature human kidney podocytes should be of great value to basic researchers and investigators in regenerative medicine who are interested in studying various types of kidney disease or trying to develop cell-based therapies,” said Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

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